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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sepsis is systemic expression of a generalized activation of the host's innate immunity as a result of varied types of insults. This expression involves a cellular inflammatory response that has both proinflammatory and antiinflammatory components, the primary trigger for which is an intracellular oxidative stress, induced by receptor-mediated transmembrane signal transduction or direct noxious injury. Sepsis reflects the interaction between pro- and anti-inflammatory intracellular mechanisms, the uncontrolled activation of which leads to cell exhaustion, organ dysfunction, and death. Successful clinical trials of novel treatments for the management of severe sepsis share a common ability to down-regulate this overall response, restoring normal proinflammatory responsiveness and mitochondrial energetic function.
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PMID:Dysregulation of the immune response in severe sepsis. 1548 37

The acronym DIC is commonly interpreted as "death is coming." This pessimistic view emphasizes the deficiency of available treatment options following diagnosis of disseminated intravascular coagulation. Clinically, DIC manifests as a systemic hemorrhagic disorder associated with widespread activation and eventual exhaustion of the coagulation system, although events underlying DIC also involve effectors of inflammation. DIC can be associated with diverse conditions including sepsis and major trauma and, when identified, signifies a significant worsening in prognosis and expected mortality. Although recent clinical studies have shown that activated protein C reduces mortality in patients with severe sepsis, there is a need for further investigation and a better understanding of the underlying mechanisms.
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PMID:Alternative treatments for disseminated intravascular coagulation. 1554 51

Cerebral edema is a life-threatening condition that develops as a result of an inflammatory reaction. Most frequently, this is the consequence of cerebral trauma, massive cerebral infarction, hemorrhages, abscess, tumor, allergy, sepsis, hypoxia, and other toxic or metabolic factors. At present, the following types of cerebral edema are differentiated: the vasogenic cerebral edema resulting from an increased permeability of the endothelium of cerebral capillaries to albumin and other plasma proteins; the cytotoxic cerebral edema resulting from the exhaustion of the energy potential of cell membranes without damage to the barrier; the hydrostatic cerebral edema resulting from disturbance of the autoregulation of cerebral blood circulation; the osmotic cerebral edema resulting from dilution of blood; and the interstitial cerebral edema resulting from acute hydrocephaly. Some authors also differentiate ischemic cerebral edema. At present, when various traumas and traumatic cerebral injuries are frequent causes of death in young people, treatment strategy for cerebral edema is of utmost importance. Monitoring of the patient's condition in the intensive care unit is a necessity. It is important to ensure proper positioning of the patient--the head should be tilted at 30 degrees in order to optimize the cerebral perfusion pressure and control of the increase in intracranial pressure. Hyperventilation should be applied. Controlled hypothermia decreases the rate of metabolism in the brain. Slightly positive fluid balance should be maintained using crystalloid or colloid (hypertonic-hyperoncotic) solutions, at the same time maintaining cerebral perfusion pressure exceeding 70 mmHg. The treatment includes administration of antihypertensive medications, nonsteroidal antiinflammatory drugs, and barbiturates. Steroids decrease the permeability of capillaries and the hemato-encephalic barrier, promoting the movement of Na(+)/K(+) ions and water through the main endothelial membrane, and therefore they are used in the treatment of vasogenic cerebral edema as well as edema caused by a cerebral tumor. Glutamate and N-methyl-D-aspartate receptor antagonists improve cerebral microcirculation and metabolism. Trometamol corrects cerebral acidosis. Extended cerebral edema is treated surgically via a bilateral decompressive craniotomy, sometimes including craniotomy of lateral and posterior fossae. The treatment of cerebral edema is complex, and positive results may be expected only if the diagnosis and the provision of assistance are timely.
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PMID:[Cerebral edema and its treatment]. 1732 53

Disseminated intravascular coagulation (DIC) is a syndrome that may complicate a variety of diseases, including malignant disease. DIC is characterized by widespread, intravascular activation of coagulation (leading to intravascular fibrin deposition) and simultaneous consumption of coagulation factors and platelets (potentially resulting in bleeding). Clinically, DIC in cancer has, in general, a less fulminant presentation than the types of DIC complicating sepsis and trauma. A more gradual, but also more chronic, systemic activation of coagulation can proceed subclinically. Eventually, this process may lead to exhaustion of platelets and coagulation factors, and bleeding (e.g. at the site of the tumour) may be the first clinical symptom indicating the presence of DIC. In some cases, the clinical presentation of DIC in cancer may be reminiscent of thrombotic microangiopathies, which is understandable in view of the role of the endothelium in both conditions. The therapeutic cornerstone of DIC is treatment of the underlying disorder, but supportive treatment specifically aimed at the haemostatic system may be required.
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PMID:Disseminated intravascular coagulation in cancer patients. 1928 79

Greater than 50% of patients with esophageal carcinoma are found to be incurable at the time of diagnosis, leaving only palliative options. Self-expanding metal stents (SEMs) are effective for relieving symptoms and complications associated with esophageal carcinoma and improving quality of life. We undertook a retrospective analysis to evaluate the experience of palliative esophageal stenting for symptomatic malignant dysphagia in our institution over a period of 7 years. Between January 1999 and January 2006, 126 patients who received SEMs for malignant dysphagia were identified using an upper gastrointestinal specialist nurse clinician database. Data were obtained from patient case notes, endoscopy, histopathology, radiology, and external agency databases. Of the 126 identified, 36 patients were excluded from the analysis. A number of variables including age, sex, presenting complaints, type of stent, indications of stenting, success or failure of stent insertion, survival rate, and complication rate were analyzed. Of the 90 patients, 55 (61%) were male and 35 (39%) were female. The mean age of patients was 70.79 (range 40-97) years. The predominant presenting complaints were dysphagia (n = 81) and weight loss (n = 48). The indication for stenting was worsening dysphagia in all patients. Tumors were confined to the distal esophagus and esophagogastric junction in 73 patients (81%), and the mid-esophagus in 17 (19%). Adenocarcinoma was identified in 61 patients (67.8%) and squamous cell carcinoma in 29 (32.2%). Stenting numbers were comparable in endoscopic and radiologic groups (47 vs. 43), with successful stent deployment in 89 patients. The 7- and 30-day mortality was 9% (n = 8) and 28% (n = 25), respectively. Comparable numbers of early deaths were seen in both radiologic (n = 13) and endoscopic (n = 12) groups. Causes of early inpatient death included hemorrhage (n = 5), pneumonia (n = 7), exhaustion (n = 2), cardiac causes (n = 3), perforation (n = 1), and sepsis (n = 1). The number of patients with complications was 41 (45.6%), 25 in the surgical group and 15 in the radiologic group; the difference was not significant (P = 0.13). The mean survival time was 92.5 (0-638) days and median survival time was 61 days. A subgroup of patients with complete dysphagia (score 4) gained a mean survival of 59 days. Those patients receiving adjuvant chemotherapy or radiotherapy survived significantly longer than those receiving stenting alone (152.8 days vs. 71.8 days). There is no significant difference in complications or survival when using endoscopic or radiologic methods to deploy SEMs in patients with inoperable esophageal cancer. Mortality is low; however, the morbidity rate is significant. Patients receiving adjuvant chemotherapy or radiotherapy, in addition to stenting, survived significantly longer than those with a stent only.
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PMID:Outcome of palliative esophageal stenting for malignant dysphagia: a retrospective analysis. 1930 13

We report a 20-year-old male who suffered smoke inhalation injury and burns covering 26% of his TBSA, including his face, dorsal chest, and both the arms. The Abbreviated Burn Severity Index was 5 (likelihood of survival 95%). He underwent burn surgery, requiring massive transfusion. Postoperatively, he appeared increasingly hyperthermic, showed respiratory exhaustion, and was neutropenic (lowest white blood cell count was 0.8 Gpt with a normal granulocyte count). He developed acute respiratory distress syndrome, renal failure, and severe inflammatory response syndrome. Aggressive ventilation patterns, intermittent prone positioning, and high-dose catecholamine therapy were performed. Hydrocortisone therapy and antibiotic prophylaxis did not improve his clinical status. He died after 12 days of septic multiple organ failure. Legal medicine autopsy identified aggressive Candida famata mycosis. The organism mainly affected the alimentary canal, and there were multiple pyemic abscesses in tissues of the heart, liver, spleen, kidneys, lungs, and meninges. Histology confirmed gastric ulcers as the source of the Candida infection. Despite the autopsy findings, all intravital specimens collected (blood, urine, and tracheal mucus) and all clinical Candida antigen tests were unsuspicious. Postoperative neutropenia may be a warning sign of severe infection even in survivable burns. Suppression of immune response and possible previous gastric Candida colonization may contribute to hazardous outcomes. However, delayed and unreliable methods to detect fungal infections remain a major problem in burn care. Occult aggressive fungal sepsis resulting in early multiple organ failure should be kept in mind.
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PMID:Fulminant, undetected Candida sepsis after an apparently survivable burn injury. 1969 26

The accelerated pace of clinical and laboratory research over the past century and application of the research findings to patient care have resulted in unprecedented survival of burned patients in all age groups. Resuscitation based on an understanding of the nature and magnitude of the multisystem response to injury now prevents burn shock; effective topical antimicrobial chemotherapy and early excision prevent wound toxemia and sepsis; biologic and bioengineered dressings compensate for the missing skin; and broad spectrum metabolic support regimens prevent exhaustion and accelerate convalescence. Rehabilitation programs have also been developed to restore physical function and permit the burn patient to reenter society as a productive individual.
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PMID:An historical perspective on advances in burn care over the past 100 years. 1979 49

1. Streptococci injected into the circulation of cats are quickly withdrawn and are found most numerously in the lung, less numerously in the liver and spleen, and in small numbers in the bone marrow, lymph nodes, muscle, and kidney. 2. The streptococci taken up by the lung are killed within 5 to 8 hours, although they remain visible in films for a number of days. In the liver they are killed less rapidly, and in the spleen a few may remain viable for a considerable period. 3. This bactericidal action may be demonstrated in pieces of excised lung but not in lung extracts, and is apparently dependent on the action of the living cell. 4. Streptococci injected into a susceptible animal, the rabbit, are also promptly removed from the circulation, but are distributed in different proportions, the liver and spleen absorbing almost as many as the lung, and the muscles also taking up an appreciable number. 5. As in the cat, the organisms taken up by the lung and liver of the living rabbit are promptly killed. Those which lodge in the muscles, however, multiply rapidly. 6. About the time that the streptococci have begun to develop in the muscles (4 to 8 hours after injection) the number in the blood stream begins to increase. 7. The increase in the blood stream is not due to exhaustion of the mechanism of their removal nor have these organisms acquired a resistance sufficient to maintain them in the blood stream of a normal animal. The septicemia, then, is probably the resuit of washing out of organisms from the infected tissues. 8. Attempts to immunize rabbits have been unsuccessful, but in certain treated animals the distribution of the organisms among the various organs approached that found in insusceptible animals; i.e., cats.
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PMID:THE EFFECT OF INJECTIONS OF HEMOLYTIC STREPTOCOCCI ON SUSCEPTIBLE AND INSUSCEPTIBLE ANIMALS. 1986 90

Failures of highly touted trials have caused experts to call for re-evaluation of the current approach toward sepsis. New research has revealed key pathogenic mechanisms; autopsy results have shown that most patients admitted to intensive care units for treatment of sepsis had unresolved septic foci at post mortem, suggesting that patients were unable to eradicate invading pathogens and were more susceptible to nosocomial organisms, or both. These results suggest that therapies that improve host immunity might increase survival. Additional work showed that cytokine production by splenocytes taken post mortem from patients who died of sepsis is profoundly suppressed, possibly because of so-called T-cell exhaustion-a newly recognised immunosuppressive mechanism that occurs with chronic antigenic stimulation. Results from two clinical trials of biomarker-guided therapeutic drugs that boosted immunity showed promising findings in sepsis. Collectively, these studies emphasise the degree of immunosuppression that occurs in sepsis, and explain why many previous sepsis trials which were directed at blocking inflammatory mediators or pathogen recognition signalling pathways failed. Finally, highly encouraging results from use of the new immunomodulatory molecules interleukin 7 and anti-programmed cell death 1 in infectious disease point the way for possible use in sepsis. We hypothesise that immunoadjuvant therapy represents the next major advance in sepsis.
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PMID:Immunosuppression in sepsis: a novel understanding of the disorder and a new therapeutic approach. 2415 94

Sepsis remains the leading cause of death in most intensive care units. Advances in understanding the immune response to sepsis provide the opportunity to develop more effective therapies. The immune response in sepsis can be characterized by a cytokine-mediated hyper-inflammatory phase, which most patients survive, and a subsequent immune-suppressive phase. Patients fail to eradicate invading pathogens and are susceptible to opportunistic organisms in the hypo-inflammatory phase. Many mechanisms are responsible for sepsis-induced immuno-suppression, including apoptotic depletion of immune cells, increased T regulatory and myeloid-derived suppressor cells, and cellular exhaustion. Currently in clinical trial for sepsis are granulocyte macrophage colony stimulating factor and interferon gamma, immune-therapeutic agents that boost patient immunity. Immuno-adjuvants with promise in clinically relevant animal models of sepsis include anti-programmed cell death-1 and interleukin-7. The future of immune therapy in sepsis will necessitate identification of the immunologic phase using clinical and laboratory parameters as well as biomarkers of innate and adaptive immunity.
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PMID:The changing immune system in sepsis: is individualized immuno-modulatory therapy the answer? 2406 65


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